N-cadherin provides a cis and trans ligand for astrotactin that functions in glial-guided neuronal migration

Significance Glial-guided neuronal migration is a key step in the histogenesis of cortical regions in the mammalian brain and requires the expression of adhesion proteins by the migrating neuron and the glial fiber. The neuronal receptor astrotactin (ASTN1) regulates glial-guided migration, but the glial ligand has long been unknown. Here we demonstrate that neuron–glia attachment and neuronal migration depend on glial expression of the neural cadherin (CDH2) and that ASTN1 promotes migration by a direct interaction with neuronal and glial CDH2. Thus, ASTN1 and CDH2 form a cis and trans asymmetric bridge complex in the migration junction that is essential for glial-guided neuronal migration.